Radionuclides which emit high LET particulate radiation (e.g., alpha particles) are very attractive for use as therapeutic radiopharmaceutical agents. Alpha particles are extremely radiotoxic to cells. Recent advances in the chemistry of labeling small organic molecules with astatine-211 have prompted renewed interest in this isotope. Astatine-211 with a half-life of 7.2 hours has excellent radiation characteristics, decaying with 42% of an alpha emission at 5.87 MeV and 58% decay by electron capture. The electron capture decay daughter, pollonium-211, is very short-lived (0.5 seconds) with an alpha emission at 7.45 MeV. Thus alpha emission is associated with 100% of the decays of astatine-211.
Due to the short half-life and high cost of astatine-211, its commercial application will require the use of a method for radiolabeling which is rapid and efficient. Additionally, consideration of the labeling personnel's safety must be of paramount concern as astatine-211 is an alpha emitting radionuclide.
Astatine-211 is a cyclotron produced radioisotope. Irradiation of a bismuth-209 target with a 28 MeV alpha beam affords astatine-211 by the alpha,2n reaction. Problems associated with the recovery of astatine from the bismuth targets have been a limitation on the development of astatine-211 radiopharmaceuticals. The most common method for recovering the astatine from a bismuth target is distillation. Astatine can be distilled from bismuth targets by heating the targets at temperatures above 600.degree. C. in a quartz tube furnace. A carrier gas sweeps through the furnace and the volatile astatine is then trapped using a variety of techniques. The most common techniques for trapping astatine are dissolution of the astatine in different solvents or adsorbing the astatine onto various surfaces such as platinum disks or silica gel. Recoveries using these methods can be highly variable.
Dissolution of the astatine by bubbling the carrier gas stream into a solvent generally is not an efficient process. In order to obtain an acceptable recovery of the astatine, a gas bubbler apparatus containing a fairly large volume of solvent is generally required. A variety of solvents have been used including water, sulfuric acid, 0.1N sodium sulfite, nitric acid/potassium dichromate solution, chloroform and methanol. Some of these solvents are not compatible with labeling of organic radiopharmaceuticals. Also, in many instances the solution concentration of astatine is quite low and a concentration step or solvent exchange step is thus required prior to labeling. Further, depending upon conditions, some of the trapped astatine can react with impurities in the solvent.
Adsorption of the astatine onto metal surfaces such as platinum is an efficient process. However a second processing step (typically a distillation) is required before the astatine can be used for labeling. Adsorption onto silica gel is another method for trapping astatine, which is then eluted from the silica gel bed using various solvents. Unfortunately, often only about 50% of the trapped astatine can be recovered from the silica gel by elution with 0.1N NaOH or sodium bisulfite solution. The volume required for maximal recovery can be prohibitively large for the efficient reaction in a subsequent step to radiolabel a molecule.
Common to most of the above methods is the requirement of secondary processing steps, e.g., distillation, concentration, solvent exchange etc., to obtain the astatine for labelling of radiopharmaceuticals. The time required for this secondary processing contributes to the overall loss of astatine from decay of the isotope. With a half-life of 7.2 hr, 9.2% of the astatine-211 is lost per hour. Significant improvements are possible if one could eliminate or combine several of the steps involved with the recovery of the isotope.